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Cytotoxic T lymphocytes and viral mutations in HTLV-I-associated myelopathy

Research Project

Project/Area Number 14570610
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKagoshima University

Principal Investigator

KUBOTA Ryuji  Kagoshima University, Faculty of Medicine, Associate professor, 医学部, 助教授 (70336337)

Co-Investigator(Kenkyū-buntansha) OSAME Mitsuhiro  Kagoshima University, Graduate School of Medical and Dental Sciences, 大学院・医歯学総合研究科, 教授 (10041435)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsHTLV-I / HTLV-I-associated myelopathy / cytotoxic T lymphocyte / mutant virus / viral evolution / 非同義置換 / HTLV-I関連脊髄症(HAM)
Research Abstract

Patients with HTLV-I-associated myelopathy(HAM)have high proviral load despite vigorous cytotoxic T lymphocytes(CTL)responses to the virus.To elucidate whether HTLV-I-speciflc CTL eliminate HTLV-I in vivo in patients with HAM and whether a mutant virus emerges and predominates during the time course in the patients, we performed a longitudinal analysis of HTLV-I proviral load, frequency and degeneracy of HTLV-I Tax specific CTL, viral sequence, and frequency of mutant virus-specific CTL in three patients with HAM.Frequency and degeneracy of CTL paralleled with the proviral load in the patients.Positive pressures were detected in 3 out of 6 sequences associated with the known CTL epitopes by analyzing synonymous and non-synonymous substitutions of viral sequences.The rate of naturally occurring mutant virus ranged from 0 to 20% in each patient, however, no mutant virus accumulated during the time course even if the virus was not recognized by the CTL. These data suggest that CTL in fact eliminate HTLV-J in vivo and that no escape variant of HTLV-I predominates during the time course.This implies that these CTL epitopes can be targets for vaccine development.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Ryuji Kubota: "Selected cytotoxic T lymphocytes with high speficity for HTLV-I in cerebrospinal fluid from a HAM/TSP patient."J Neurovirol. 8(1). 53-57 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ryuji Kubota: "Degenerate specificity of HTLV-I-specific CD8+ T cells during viral relplication in patients with HTLV-I-associated myelopathy (HAM/TSP)."Blood. 101(8). 3074-3081 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshitaka Furukawa: "Human T-cell lymphotropic virus type I (HTLV-I)-related clinical and laboratory findings for HTLV-I-infected blood donors."J Acquir Immune Defic Syndr. 32(3). 328-334 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mineki Saito: "Decreased human T lympohotropic virus type I (HTLV-I) provirus load and lateration in T cell phenotype after interferon-alpha therapy...."J Infect Dis. 189(1). 29-40 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 納光弘: "HAMの病態と治療"日本内科学会雑誌. 92(9). 65-74 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ryuji Kubota et al.: "Selected cytotoxic T lymphocytes with high specificity for HTLV-I in cerebrospinal fluid from a HAM/TSP patient."J Neurovirol.. 8(1). 53-57 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ryuji Kubota et al.: "Degenerate specificity of HTLV-I-specific CD8+T cells during viral replication in patients with HTLV-I-associated myelopathy(HAM/TSP)."Blood.. 101(8). 3074-3081 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshitaka Furukawa et al.: "Human T-cell lymphotropic virus type I(HTLV-I)-related clinical and laboratory findings for HTLV-I-infected blood donors."J Acquir Immune Defic Syndr.. 32(3). 328-334 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mineki Saito et al.: "Decreased human T lymphotropic virus type I(HTLV-I)provirus load and alteration in T cell phenotype after interferon-alpha therapy for HTLV-I-associated myelopahty/tropical spastic paraparesis."J Infect Dis.. 189(1). 29-40 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitsuhiro Osame et al.: "Physiopathology and treatment of HAM"Nippon Naika Gakkai Zasshi.. 92(9). 65-74 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ryuji Kubota: "Degenerate specificity of HTLV-I-specific CD8+ T cells during viral replication in patients with HTLV-I-associated myelopathy (HAM/TSP)."Blood. 101(8). 3074-3081 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshitaka Furukawa: "Human T-cell lymphotropic virus type I (HTLV-I)-related clinical and laboratory findings for HTLV-I-infected blood donors."J Acquir Immune Defic Syndr. 32(3). 328-334 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mineki Saito: "Decreased human T lymphotropic virus type I (HTLV-I) provirus load and alteration in T cell phenotype after interferon-alpha therapy...."J Infect Dis. 189(1). 29-40 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 納光弘: "HAMの病態と治療"日本内科学会雑誌. 92(9). 65-74 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ryuji Kubota: "Degenerate specificity of HTLV-I-specific CD8+ T cells during viral replication in patients with HTLV-I-associated myelopathy (HAM/TSP)"Blood. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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